Genomic DNA microarray based comparative genomic hybridization (CGH) has the potential to perform faster, more efficiently and cheaper than traditional CGH methods, which rely on comparative hybridization on individual metaphase chromosomes. Array-based CGH uses immobilized nucleic acids arranged as an array on a biochip or a microarray platform. The so-called array or chip CGH approach can provide DNA sequence copy number information across the entire genome in a single, timely, cost-effective and sensitive procedure. The resolution of chip CGH is primarily dependent upon the number, size and map positions of the DNA elements within the array. Bacterial artificial chromosomes, or BACs, can each accommodate on average about 150 kilobases (kb) of cloned genomic DNA, and are often used in the production of the array.
Array CGH uses genomic DNA from cells of a series of samples to be compared, for example, a test sample and a reference sample (e.g., a sample from cells ideally free of known chromosomal aberrations). The two samples are labeled with different fluorescent dyes, and are mixed and co-hybridized to immobilized nucleic acids, e.g., BACs, or other clones that contain a set of cloned genomic DNA fragments that collectively include a pre-determined portion of a genome or an entire genome. The resulting co-hybridization produces a fluorescently labeled array, and the extent of fluorescence of each of the dyes on each spot reflects competitive hybridization of sequences in the test and reference genomic DNAs to the homologous sequences within the immobilized nucleic acids. Theoretically, the copy number ratio of homologous sequences in the test and reference genomic DNA samples should be directly proportional to the ratio of their respective fluorescent signal intensities at discrete BACs within the array. The versatility of the approach allows detection of constitutional variations in DNA copy number in clinical cytogenetic samples such as amniotic samples, chorionic villus samples (CVS), blood samples and tissue biopsies. It also allows detection of somatically acquired genomic changes in tumorigenically altered cells, for example, from bone marrow, blood or solid tumor samples.